24 Prevention of Gastric Ulcers Mohamed Morsy and Azza El-Sheikh Pharmacology Department, Minia University Egypt 1. Introduction Upper gastrointestinal tract integrity is dependent upon the delicate balance between naturally occurring protective factors as mucus or prostaglandins and damaging factors as hydrochloric acid present normally in the digestive juices. An imbalance causes peptic ulcer formation and destruction of gastrointestinal tract mucosal lining. Ulcer may develop in the esophagus, stomach, duodenum or other areas of elementary canal. In women, gastric ulcers are more common than duodenal ulcers, while in men the opposite is true. The ulcer irritates surrounding nerves and causes a considerable amount of pain. Obstruction of the gastrointestinal tract may occur as a result of spasm or edema in the affected area. The ulcer may also cause the erosion of major blood vessels leading to hemorrhage, hematemesis and/or melena. Deep erosion of the wall of the stomach or the intestine may cause perforation and peritonitis, which is a life-threatening condition needing emergency intervention. Duodenal ulcers are almost always benign but stomach ulcers may turn malignant. Although mortality rates of peptic ulcer are low, the high prevalence of the disease, the accompanying pain and its complications are very costly. The ongoing rapidly expanding research in this field provides evidence suggesting that, with therapeutic and dietetic advances, gastric ulcer may become preventable within the next decade. This could be achieved by strengthening the defense mechanisms of the gastric mucosa and, in parallel, limiting the aggression of predisposing factors causing gastric ulceration. The defenses of the gastric mucosa are incredibly efficient under normal mechanical, thermal or chemical conditions. These defenses can endure insults from food, gastric enzymes and acid secretion. Even trauma caused by a biopsy wound is dealt with and can heal relatively fast, within hours. However, under certain condition, some risk factors may contribute to mucosal injury and initiation of gastric ulcer, as psychological stress, increased hydrochloric acid secretion, Zollinger Ellison syndrome and family history of gastric ulcer. Conditions associated with increased risk of gastric ulcer include also chronic disorders as liver cirrhosis, chronic obstructive pulmonary disease, renal failure, organ transplantation and rheumatoid arthritis. In addition, severe physical stress as in case of burns, major surgery or head trauma may also contribute as risk factors. Avoidable risk factors that may predispose to gastric ulcer include smoking, high consumption of alcohol and intake of some medications as non-steroidal anti-inflammatory drugs. Some factors are thought to aggravate already established gastric ulcer, but are no longer considered risk factors predisposing to it, as ingestion of too hot or cold foods or drinks, eating spicy food and intake of caffeine. The key cause of gastric ulcer is now known www.intechopen.com 438 Peptic Ulcer Disease to be the infection by a certain gram negative bacterium called Helicobacter pylori. Although the mechanism by which the infection by this bacterium leads to ulcer formation is not yet fully understood, it is believed that infection decreases the normal immunity of the gastrointestinal tract wall, which in turn weakens the mucosa and makes it vulnerable to ulceration under the acidic effect of gastric secretions. Avoiding risk factors is the first line in prevention of gastric ulcer. Smoking cessation and alcoholic consumption minimization may help in reducing the risk of ulcer formation. In addition, sanitary food and drinking habits to avoid infection with Helicobacter pylori may help in ameliorating the initiation of gastric ulcer and its recurrence. Therapeutic interventions to eradicate Helicobacter pylori can also prevent ulcer formation and its transformation into gastric cancer, one of the major complications of chronic gastric ulcer. Avoiding unnecessary intake of ulcer-inducing over-the-counter medications may help in reducing the prevalence of gastric ulcers. Active therapeutic measures can aid in preventing gastric ulcers in predisposed groups and in patients with healed gastric ulcer to avoid its recurrence. Such therapeutic interventions may be of natural herbal sources or medicinal drugs. A number of traditional anti-ulcer drugs may be used in prevention as well as in treatment of gastric ulcer. Proton pump inhibitors, histamine H2 receptor antagonists and mucosal protective agents can thus all be used as protective drugs against initiation of gastric ulcer in predisposed groups as well as prevention of remittent attacks. Recent investigations showed that a number of drugs, other than traditional anti-ulcer medications, can help in prevention of gastric ulcer formation. Herbal compounds can also protect against gastric ulcer and they have the advantage of being safer, cheaper and usually having limited, if any, side effects. In this chapter, a collection of updated recent information published about gastric ulcer protection is gathered. Information in this chapter can be considered as guidelines for clinical practice to direct medical personnel perception to preferred approaches to prevent gastric ulcer as established by scientifically valid research. Making such information available may also increase public awareness of preventive means of gastric ulcer, which may aid in decreasing the suffering of a large number of populations exposed to the disease worldwide. 2. Avoidance of gastric ulcer risk factors The best and cheapest method to prevent gastric ulceration is the avoidance of risk factors resulting in the occurrence of the disease. Avoiding Helicobacter pylori infection, alternation of life style and substitution of ulcer-inducing medications with less harmful drugs can thus contribute largely to prevent gastric ulcer disease (Fig. 1). Unfortunately, some risk factors are unavoidable. One of the strongest risk factors for initiation of a gastric ulcer is the presence of prior ulcer disease with history of ulcer complications as previous perforation or hemorrhage. Zollinger-Ellison Syndrome is another unavoidable cause of gastric ulceration. In this syndrome, tumors producing gastrin hormone (gastrinomas) in the pancreas and duodenum stimulate gastric acid secretion. The large amounts of excess acid produced cause gastro-intestinal ulceration. Ulcers may form in the stomach, duodenum, jejunum or other atypical sites in the elementary tract. The incidence of this disease is less than 1% and men are more affected than women. The syndrome is suspected in patients with ulcers who are not infected with Helicobacter pylori and who have no history of non-steroidal anti- inflammatory drugs use. Diagnosis is confirmed by measurement of serum gastrin hormone www.intechopen.com Prevention of Gastric Ulcers 439 Helicobacter pylori Diet Stress Smoking Alcohol Drug Life style induction risk factors Fig. 1. Methods of prevention of gastric ulcer: Avoiding risk factors as Helicobacter pylori, drug-induced ulcer by medications as non-steroidal anti-inflammatory drugs and performance of life style changes. levels which is usually very high, reaching above 1000 pg/ml (normal level is < 100 pg/ml). Diarrhea may occur before ulcer symptoms. Gastro-esophageal reflux disease may occur and its complications may include narrowing due to strictures of the esophagus. Ulcers associated with this syndrome are usually persistent and difficult to treat. In the past, removing the stomach was the only option for treatment. Nowadays, treatment includes removing the tumors only and therapeutic suppression of acid secretion. Other unavoidable factors associated with higher incidence of gastric ulcer include sex, as there is higher prevalence of the disease among women then men. People over age 60 years old are also more prone to gastric ulcer disease. In addition, ethnic backgrounds as African- Americans or Hispanics have 2-fold higher risk in developing gastric ulcer. Furthermore, patients suffering from other diseases as congestive heart failure have higher incidence of having gastric ulcer as well. Type O blood group has also been associated with increased incidence of the disease. Genetics is another unavoidable risk factor of gastric ulcer. Pepsinogen C gene polymorphism, for example, is significantly associated with development of gastric ulcer (Sun et al., 2009). Other relatively rarer predisposing factors to development of gastric ulcer includes Crohn’s disease of the stomach, eosinophilic gastritis, systemic mastocytosis, radiation damage and viral infections by cytomegalovirus or herpes simplex (Malfertheiner et al., 2009). www.intechopen.com 440 Peptic Ulcer Disease 2.1 Helicobacter pylori as a risk factor for gastric ulcer Infection with Helicobacter pylori is the most well-defined risk factor for the development of peptic ulcers. The two Australian scientists who identified Helicobacter pylori as the main cause of stomach ulcers in 1982 were awarded the Nobel Prize in Medicine in 2005 for this discovery. Helicobacter pylori bacteria are found in about 50% of people with gastric ulcer disease. Inflammation of the stomach and stomach ulcers result from the infection by these bacteria, as their corkscrew shape enables them to penetrate the mucus layer of the stomach so that they can attach themselves to the lining. The surfaces of the cells lining the stomach contain a protein, called decay-accelerating factor,